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Original Research Open Access

PAX-Interacting Protein 1 (PTIP) Promotes Apoptosis

  • 1Department of Biology, Arts and Sciences, New York University in Shanghai, Shanghai 200122, China
  • 2Department of Molecular Science and Technology, Advanced College of Bio-Convergence Engineering, Ajou University 206 Worldcup-ro, Yeongtong-gu, Suwon 16499, South Korea
  • 3Molecular Biosciences, University of Texas at Austin, 1 University Station A5000, Austin, TX 78712, USA
+ Affiliations - Affiliations

Corresponding Author

Haley O. Tucker, haleytucker@austin.utexas.edu

Received Date: September 18, 2025

Accepted Date: October 10, 2025

Abstract

PAX-interacting protein 1 (PTIP/PAXIP1) was discovered and initially characterized over three decades ago as a 1,056 amino acid-containing protein with six tandem BReast cancer C-Terminal (BRCT) repeats. PTIP functions broadly to catalyze histone methylation in DNA damage repair and within the hematopoietic lineage, to promote immunoglobulin variable region (variable, diversity, joining [VDJ]) and class switch recombination (CSR). In this report, we show that a fraction of PTIP is actively transported from the nucleus to mitochondria resulting in their aggregation, release of cytochrome c into the cytoplasm and cellular apoptosis. Deletion of an N-terminal glutamine-rich region (QR), mutation of a conserved threonine within BRCT3 and truncation of the C-terminal BRCT5 domain each significantly reduced apoptosis as well as its previously documented G2/M cell cycle function. This is the first report to identify a mitochondrial-based apoptotic mechanism employed by the PTIP transcription factor.

Keywords

Breast cancer C-Terminal, Class switch recombination, DNA, Immunoglobulin

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